Netrin-1 is currently one of the most highly studied axon guidance factors. Netrin-1 is widely expressed in the embryonic central nervous system, and together with the deleted in colorectal cancer and uncoordinated lo...Netrin-1 is currently one of the most highly studied axon guidance factors. Netrin-1 is widely expressed in the embryonic central nervous system, and together with the deleted in colorectal cancer and uncoordinated locomotion-5 homolog B receptors, netrin-1 plays a guiding role in the construction of neural conduction pathways and the directional migration of neuronal cells. In this study, we established a rat middle cerebral artery ischemia reperfusion model using the intraluminal thread technique. Immunofluorescence microscopy showed that the expression of netrin-1 and deleted in colorectal cancer in the ischemic penumbra was upregulated at 1 day after reperfusion, reached a peak at 14 days, and decreased at 21 days. There was no obvious change in the expression of uncoordinated locomotion-5 homolog B during this time period. Double immunofluorescence labeling revealed that netrin-1 was expressed in neuronal cells and around small vessels, but not in astrocytes and microglia, while deleted in colorectal cancer was localized in the cell membranes and protrusions of neurons and astrocytes. Our experimental findings indicate that netrin-1 may be involved in post-ischemic repair and neuronal protection via deleted in colorectal cancer receptors.展开更多
目的探讨m^(6)A去甲基化酶烷基化修复蛋白B同源物5(alkylation repair protein B homolog 5,ALKHB5)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法收集2009年1月至2013年8月在桂林医学院附属医院接受肝癌切...目的探讨m^(6)A去甲基化酶烷基化修复蛋白B同源物5(alkylation repair protein B homolog 5,ALKHB5)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法收集2009年1月至2013年8月在桂林医学院附属医院接受肝癌切除术的80例HCC患者的癌组织及其癌旁组织(距病灶>3 cm)的石蜡包埋标本,采用免疫组化法检测ALKBH5的表达水平,并分析其与HCC患者临床病理特征及与预后的关系。结果在HCC组织中ALKBH5高表达的患者比例明显低于癌旁组织(P=0.001),且与肿瘤大小和血清甲胎蛋白(α⁃fetoprotein,AFP)水平相关(均P<0.05)。Kaplan⁃Meier生存分析显示ALKBH5低表达组患者的总生存期(P=0.011)和无复发生存期(P=0.012)均缩短,多因素Cox回归分析显示ALKBH5低表达是影响HCC患者总生存期(HR=1.965,95%CI:1.029~3.751,P=0.041)和无复发生存期(HR=2.201,95%CI:1.046~4.629,P=0.038)的独立危险因素。结论ALKBH5在HCC组织中表达下调且低表达患者预后不良,ALKBH5可能是HCC潜在的预后评估指标及治疗靶点。展开更多
Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regu...Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular model.Cardiac echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac function.In CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione) peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 stimulation.Let-7a-5p was enriched in hucMSCs-exo,and the inhibitory ffect of hucMSCs-exoa-ie-pmimo on CVB3-induced ferroptosis was higher than that of hucMSCs-exommie N(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)decreased.Let-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 protein.Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators.Meanwhile,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe^(2+)increased.In conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 expression.Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.展开更多
目的:探讨绒毛组织中轴突导向因子(Netrin-1)及其受体结直肠癌缺失基因(deleted in colorectal cancer,DCC)和非协调性分子5同源蛋白B(uncoordinated-5-homolog B,UNC5B)的表达及其与胚胎停止发育的关系。方法:采用免疫组织化学PV法检...目的:探讨绒毛组织中轴突导向因子(Netrin-1)及其受体结直肠癌缺失基因(deleted in colorectal cancer,DCC)和非协调性分子5同源蛋白B(uncoordinated-5-homolog B,UNC5B)的表达及其与胚胎停止发育的关系。方法:采用免疫组织化学PV法检测20例正常早期妊娠绒毛(对照组)、25例早期胚胎停止发育绒毛(实验组)组织中Netrin-1及其受体DCC、UNC5B的表达情况。结果:Netrin-1在对照组的阳性表达率为95.00%,实验组的阳性表达率为76.00%,组间差异有统计学意义(P<0.01)。DCC在对照组阳性表达率为95.00%,实验组阳性表达率为32.00%,组间差异有统计学意义(P<0.01)。UNC5B在对照组阳性表达率为55.00%,实验组阳性表达率为96.00%,组间差异有统计学意义(P<0.01)。对照组Netrin-1、DCC和UNC5B三者两两间的表达无显著相关性。实验组DCC和Netrin-1的表达间呈显著负相关(r=-0.227,P<0.01),DCC和UNC5B的表达间呈显著正相关(r=0.151,P<0.05)。Netrin-1和UNC5B的表达间无显著相关性(r=-0.065,P=0.303)。结论:Netrin-1及其受体DCC、UNC5B的异常表达可能与早期胚胎停止发育发生有关;三者可能通过协同作用影响早期胚胎发育过程中胎盘血管的形成,导致胚胎停止发育。展开更多
基金supported by the Science and Technology Program of Suzhou Industrial Park in China
文摘Netrin-1 is currently one of the most highly studied axon guidance factors. Netrin-1 is widely expressed in the embryonic central nervous system, and together with the deleted in colorectal cancer and uncoordinated locomotion-5 homolog B receptors, netrin-1 plays a guiding role in the construction of neural conduction pathways and the directional migration of neuronal cells. In this study, we established a rat middle cerebral artery ischemia reperfusion model using the intraluminal thread technique. Immunofluorescence microscopy showed that the expression of netrin-1 and deleted in colorectal cancer in the ischemic penumbra was upregulated at 1 day after reperfusion, reached a peak at 14 days, and decreased at 21 days. There was no obvious change in the expression of uncoordinated locomotion-5 homolog B during this time period. Double immunofluorescence labeling revealed that netrin-1 was expressed in neuronal cells and around small vessels, but not in astrocytes and microglia, while deleted in colorectal cancer was localized in the cell membranes and protrusions of neurons and astrocytes. Our experimental findings indicate that netrin-1 may be involved in post-ischemic repair and neuronal protection via deleted in colorectal cancer receptors.
文摘目的探讨m^(6)A去甲基化酶烷基化修复蛋白B同源物5(alkylation repair protein B homolog 5,ALKHB5)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法收集2009年1月至2013年8月在桂林医学院附属医院接受肝癌切除术的80例HCC患者的癌组织及其癌旁组织(距病灶>3 cm)的石蜡包埋标本,采用免疫组化法检测ALKBH5的表达水平,并分析其与HCC患者临床病理特征及与预后的关系。结果在HCC组织中ALKBH5高表达的患者比例明显低于癌旁组织(P=0.001),且与肿瘤大小和血清甲胎蛋白(α⁃fetoprotein,AFP)水平相关(均P<0.05)。Kaplan⁃Meier生存分析显示ALKBH5低表达组患者的总生存期(P=0.011)和无复发生存期(P=0.012)均缩短,多因素Cox回归分析显示ALKBH5低表达是影响HCC患者总生存期(HR=1.965,95%CI:1.029~3.751,P=0.041)和无复发生存期(HR=2.201,95%CI:1.046~4.629,P=0.038)的独立危险因素。结论ALKBH5在HCC组织中表达下调且低表达患者预后不良,ALKBH5可能是HCC潜在的预后评估指标及治疗靶点。
基金supported by the China Postdoctoral Science Foundation(No.2022M712252)the Natural Science Foundation of Sichuan Province,China(No.2023NSFSC1634).
文摘Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular model.Cardiac echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac function.In CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione) peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 stimulation.Let-7a-5p was enriched in hucMSCs-exo,and the inhibitory ffect of hucMSCs-exoa-ie-pmimo on CVB3-induced ferroptosis was higher than that of hucMSCs-exommie N(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)decreased.Let-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 protein.Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators.Meanwhile,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe^(2+)increased.In conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 expression.Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.
文摘目的:探讨绒毛组织中轴突导向因子(Netrin-1)及其受体结直肠癌缺失基因(deleted in colorectal cancer,DCC)和非协调性分子5同源蛋白B(uncoordinated-5-homolog B,UNC5B)的表达及其与胚胎停止发育的关系。方法:采用免疫组织化学PV法检测20例正常早期妊娠绒毛(对照组)、25例早期胚胎停止发育绒毛(实验组)组织中Netrin-1及其受体DCC、UNC5B的表达情况。结果:Netrin-1在对照组的阳性表达率为95.00%,实验组的阳性表达率为76.00%,组间差异有统计学意义(P<0.01)。DCC在对照组阳性表达率为95.00%,实验组阳性表达率为32.00%,组间差异有统计学意义(P<0.01)。UNC5B在对照组阳性表达率为55.00%,实验组阳性表达率为96.00%,组间差异有统计学意义(P<0.01)。对照组Netrin-1、DCC和UNC5B三者两两间的表达无显著相关性。实验组DCC和Netrin-1的表达间呈显著负相关(r=-0.227,P<0.01),DCC和UNC5B的表达间呈显著正相关(r=0.151,P<0.05)。Netrin-1和UNC5B的表达间无显著相关性(r=-0.065,P=0.303)。结论:Netrin-1及其受体DCC、UNC5B的异常表达可能与早期胚胎停止发育发生有关;三者可能通过协同作用影响早期胚胎发育过程中胎盘血管的形成,导致胚胎停止发育。
